0 avis
Development, Synthesis and Antiprotozoal Assessment of New Substituted Diquinolinyl-Pyridine Derivatives as Antiparasitic Agents by Potential G-4 Binding
Archive ouverte
Edité par CCSD -
International audience. In order to fight malaria, a public health problem for which nearly half of the world's population is at risk and responsible a life-threatening disease primarily found in tropical countries and for which the estimated number of deaths stood at 619 000 in 2021,an original strategy is to design and synthesize quinoline-based drugs that are not recognized by the protein system involved in thedrug efflux. Thus, a series of new 2,6-di-(carbamoyl-2-quinolinyl)pyridine derivatives was considered, synthesized, and evaluated invitro against three parasites (Plasmodium falciparum, Leishmania donovani and Trypanosoma brucei brucei). Pharmacological resultsshowed antiparasitic activity with IC 50 values in the sub and μM range. The in vitro cytotoxicity of these new diquinolinyl-pyridinederivatives was evaluated on human HepG2 cells. The diquinolinyl-pyridine 1e was found as the most potent antimalarial candidatewith a ratio of cytotoxic to antiprotozoal activities of 73.5 against the P. falciparum CQ-resistant strain W2. Moreover, derivative3b was also identified as the most potent antiparasitic compound with a selectivity index (SI) of 21.48 on 3D7 P. falciparum CQ-sensitive strain. In addition, the 2,6-di-(carbamoyl-2-quinolinyl)pyridines 2c and 3b were also identified as the most interestingantitrypanosomal candidate drugs with selectivity index (SI) of 75.9 and 38.94, respectively on T. brucei brucei strain. It has beenpreviously described that the telomeres of parasites P. falciparum and Trypanosoma could be considered as potential targets of thiskind of nitrogen heterocycles, thus the ability of these new derivatives to stabilize the parasitic telomeric G-quadruplexes have beenmeasured through a FRET melting assay.
Consulter en ligne
Suggestions
Du même auteur
